Antiproliferative mechanisms of the flavonoids 2,2'-dihydroxychalcone and fisetin in human prostate cancer cells.
We have previously demonstrated the antiproliferative effect of two flavonoids-2,2'-dihydroxychalcone (DHC), a novel synthetic flavonoid, and fisetin, a naturally occurring flavonol-in prostate cancer cells. In this study, we further examine the mechanisms of these compounds on survival and prolifer...
| Published in: | Nutrition & Cancer Vol. 62; no. 5; pp. 668 - 682 |
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| Main Authors: | , , , , , , |
| Format: | equations & formulas research tables/charts Journal Article |
| Published: |
Taylor & Francis Ltd
Jul2010
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| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=105038089&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 105038089 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 01635581 7MS jtl: Nutrition & Cancer issn: 01635581 maglogo: N pubinfo: dt: Jul2010 vid: 62 iid: 5 pid: 377 pub: Taylor & Francis Ltd place: Philadelphia, Pennsylvania artinfo: ui: 105038089 2010696066 10.1080/01635581003605524 NLM20574928 105038089 ppf: 668 ppct: 14 formats: fmt: @attributes: type: P tig: atl: Antiproliferative mechanisms of the flavonoids 2,2'-dihydroxychalcone and fisetin in human prostate cancer cells. aug: au: Haddad AQ Fleshner N Nelson C Saour B Musquera M Venkateswaran V Klotz L affil: Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada sug: subj: Cell Physiology Flavonoids Therapeutic Use Prostatic Neoplasms Physiopathology Apoptosis Biological Assay Methods Cell Cycle Physiology Funding Source Human Immunoblotting Methods Neoplasms Nutrition Polymerase Chain Reaction Methods Prostatic Neoplasms Mortality Proteins Physiology Survival ab: We have previously demonstrated the antiproliferative effect of two flavonoids-2,2'-dihydroxychalcone (DHC), a novel synthetic flavonoid, and fisetin, a naturally occurring flavonol-in prostate cancer cells. In this study, we further examine the mechanisms of these compounds on survival and proliferation pathways. DHC and fisetin (1-50 [mu]M) caused a dose-dependent reduction in viability, a concomitant increase in apoptosis in PC3 cells at 72 h, and a decrease in clonogenic survival at 24 h treatment. DHC was considerably more potent than fisetin in these cytotoxicity assays. The mechanism of accelerated cellular senescence was not activated by either compound in PC3 or lymph node carcinoma of the prostate (LNCaP) cells. Gene expression alterations in PC3 and LNCaP cells treated with 15 [mu]M DHC and 25 [mu]M fisetin for 6 to 24 h were determined by oligonucleotide array. Amongst the most highly represented functional categories of genes altered by both compounds was the cell cycle category. In total, 100 cell cycle genes were altered by DHC and fisetin including 27 genes with key functions in G2/M phase that were downregulated by both compounds. Other functional categories altered included chromosome organization, apoptosis, and stress response. These results demonstrate the multiple mechanisms of antitumor activity of DHC and fisetin in prostate cancer cells in vitro. pubtype: Academic Journal doctype: equations & formulas research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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